Comparative Immunogenicity of Respiratory Virus Vaccines (CIRV2) Study

NCT07287137 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: IDCRP-154
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

CIRV2 is a Phase IV randomized, open-label, trial of FDA-approved COVID-19 and/or influenza vaccines (no more than minimal risk) with longitudinal follow-up. In 2025 CIRV2 will compare immunogenicity and reactogenicity of the recombinant Novavax COVID-19 vaccine and the mRNA Pfizer-BioNTech COVID-19 vaccine.

Conditions

COVID 19; Respiratory Virus Infection; Respiratory Virus Infections; Influenza; Respiratory Virus; Respiratory Viruses

Keywords

COVID-19 vaccine; Influenza vaccine; Respiratory virus vaccine; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• Variant-specific immune responses

  The primary endpoint is variant-specific immune response (magnitude and breadth) to licensed recombinant and mRNA COVID-19 products administered to healthy adult MHS beneficiaries. This will include quantifying the magnitude of binding and neutralizing antibodies to the vaccine variants and to the dominant variant present one month post-vaccination. Specifically, we will test neutralizing titers (defined as the inverse serum dilution causing a 50% reduction in relative light units in a pseudovirus neutralization assay) and IgG binding antibody levels (measured in arbitrary units) against the following SARS-CoV-2 variants: NB.1.8.1 and XFG (predominant circulating strains in fall 2025), JN.1 and LP.8.1 (vaccine strains), and Wuhan-1 (ancestral strain).

  IgG binding antibody levels and neutralizing antibody titers will be assessed on serum samples obtained just prior to vaccination and 30 days (+/- 10 days) after vaccination.

Other Outcomes (4)

• Vaccine reactogenicity and other incident adverse events (compared between two licensed COVID-19 platforms - recombinant and mRNA)

  Reactogenicity and other incident adverse events will be assessed through 9 months after vaccination.

• Frequency of participant-reported test positive (antigen and/or PCR) SARS-CoV-2 infections (compared between two licensed COVID-19 platforms - recombinant and mRNA) during the eight months following COVID vaccination and assessment of their symptom patte

  Through 9 months after vaccination.

• Salivary and nasopharyngeal IgG and IgA antibody levels to vaccine SARS-CoV-2 strain and dominant SARS-CoV-2 circulating strain at 30 days post vaccination

  These antibody tests will be conducted on biosamples obtained just prior to vaccination and 30 days (+/- 10 days) after vaccination.

Study Arms (2)

For fall of 2025, Arm 1 of the study will be the Pfizer-BioNTech mRNA COVID-19 vac

ACTIVE COMPARATOR

Arm 1 of the study will be Pfizer-BioNTech mRNA COVID-19 vaccine

Drug: Pfizer-BioNTech mRNA COVID-19 vaccine

For fall of 2025, Arm 2 of the study will be the Novavax recombinant protein vaccine

ACTIVE COMPARATOR

Arm 2 of the study will be the Novavax recombinant protein vaccine

Drug: Novavax recombinant protein vaccine

Interventions

Novavax recombinant protein vaccine DRUG

Recombinant protein vaccine

For fall of 2025, Arm 2 of the study will be the Novavax recombinant protein vaccine

Pfizer-BioNTech mRNA COVID-19 vaccine DRUG

COVID-19 Vaccine, mRNA

For fall of 2025, Arm 1 of the study will be the Pfizer-BioNTech mRNA COVID-19 vac

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Have a history of any of the following risk factors for severe COVID:
• Asthma
• Physical inactivity (defined as \<150 mins of moderate activity per week or \<75 mins of vigorous activity per week)
• HIV with CD4 count ≥ 500 cells/ul
• Current or prior smoker
• Depression or other mood disorder
• Schizophrenia spectrum disorder
• Cerebrovascular disease
• Heart failure
• Coronary artery disease
• Cardiomyopathy
• Pulmonary embolism
• Pulmonary hypertension
• Cystic fibrosis

You may not qualify if:

• History of severe allergy or severe adverse reaction such as myocardial inflammation to any component of the mRNA COVID-19 vaccines or the Novavax recombinant COVID-19 vaccine
• Received a COVID-19 vaccine in the last 3 months.
• Tested positive for COVID-19 in the past 3 months.
• \- Presence of fever, cough, chills, shortness of breath, runny nose, or sore throat today on day of screening/enrollment visit.
• Active use of immune modulating medications.
• \- Defined as active use of chronic immune modulating medications such as systemic corticosteroids at a dose equivalence of 20 mg prednisone or greater daily for over one month, chemotherapy, cytokine inhibitors, or agents that reduce T cell or B cell numbers or function.
• Diagnosed with immunocompromised stated.
• \- Defined as: presence of a disease that is actively causing severe immune suppression or history of prior splenectomy (removal of spleen).
• Diabetes with the most recent HgbA1C ≥ 7.5.
• Stage III or greater chronic kidney disease
• \- Defined as estimated glomerular filtration rate \< 60 ml/min/1.73m2)
• Obesity with a BMI ≥ 40
• HIV with a CD4 cell count \< 500 cells/ul
• History of solid organ or bone marrow transplant.
• Active malignancy

Sponsors & Collaborators

• Food and Drug Administration (FDA): collaborator
• Henry M. Jackson Foundation for the Advancement of Military Medicine: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Walter Reed National Military Medical Center

Bethesda, Maryland, 20814, United States

Location

Related Publications (32)

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MeSH Terms

Conditions

COVID-19; Influenza, Human

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Orthomyxoviridae Infections

Study Officials

• Edward Mitre, MD

  Uniformed Services University of the Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open-label, with concealment of vaccine allocation until time of vaccination and blinding of all laboratory personnel conducting antibody assays.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Enrollment of 50-54 individuals to receive the vaccine (up to 27 per arm) per year.

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: December 17, 2025
• Study Start: November 12, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

US (1)